title: The α4 nicotinic receptor promotes CD4+ T-cell proliferation and a helper T-cell immune response.
abstract: Smoking is a common addiction and a leading cause of disease. Chronic nicotine exposure is known to activate nicotinic acetylcholine receptors (nAChRs) in immune cells. We demonstrate a novel role for α4 nAChRs in the effect of nicotine on T-cell proliferation and immunity. Using cell-based sorting and proteomic analysis we define an α4 nAChR expressing helper T-cell population (α4(+)CD3(+)CD4(+)) and show that this group of cells is responsive to sustained nicotine exposure. In the circulation, spleen, bone marrow, and thymus, we find that nicotine promotes an increase in CD3(+)CD4(+) cells via its activation of the α4 nAChR and regulation of G protein subunit o, G protein regulated-inducer of neurite outgrowth, and CDC42 signaling within T cells. In particular, nicotine is found to promote a helper T cell 2 adaptive immunologic response within T cells that is absent in α4(-/-) mice. We thus present a new mechanism of α4 nAChR signaling and immune regulation in T cells, possibly accounting for the effect of smoking on the immune system.
authors.affiliation: Department of Molecular Neuroscience, Krasnow Institute for Advanced Study, George Mason University, Fairfax, Virginia (J.C.N., S.C., N.K.); and Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia (P.M., M.I.D.).
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Nordman
authors.forename: Pretal
authors.initials: P
authors.lastname: Muldoon
authors.forename: Sarah
authors.initials: S
authors.lastname: Clark
authors.forename: M Imad
authors.initials: MI
authors.lastname: Damaj
authors.forename: Nadine
authors.initials: N
authors.lastname: Kabbani
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D017252:CD3 Complex / Q000378:metabolism; D015704:CD4 Antigens / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016207:Cytokines; D009538:Nicotine; D011978:Receptors, Nicotinic; D020764:cdc42 GTP-Binding Protein